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Molecular and Cellular Neurosciences

Laboratory of Developmental Neurobiology

Jun Motoyama,Ph.D.
The human brain has about 14 billion neurons and over ten times that number of glia cells that exist within a highly complex structure that performs multiple functions. From the moment it is fertilized, an egg repeatedly divides and differentiates over the course of gestation. Eventually, the brain forms. That process of brain formation is our focus, through which we hope to understand the brain. A fertilized egg will repeatedly divided to become first an embryo, then a fetus. Part of the embryo forms a tube, called the neural tube, that is the start of the central nervous system: brain and spinal cord. The developmental from the neural tube to the brain may help explain the brain. We are investigating the mechanisms that determine the midline structure of the brain, the first crucial step in development. We are also trying to understand how neural stem cells emerge and develop. A secreted protein called sonic hedgehog (Shh) currently commands our attention. This protein, which is essential for healthy brain development, maintains brain functions after birth. Constructing tissue with a large number of cells requires coordination and role allocation among the various groups of cells. For brain development, it is becoming clear that cell-to-cell interactions are supported by many molecular events are essential to that process. Shh may participate in those intercellular interactions. Efforts by our laboratory and others have shown Shh's roles in determining the midline structure and in directing the development of neural stem cells. We would like to reveal the functions and roles of other molecules involved in Shh protein signaling cascade that leads to the proper development of brain tissue.
Jun Motoyama,Ph.D.
Fig.1:Expression of Sonic hedgehog (Shh) protein and the determination of the midline structure in mouse embryo
Fig.1 : Expression of Sonic hedgehog (Shh) protein and the determination of the midline structure in mouse embryo
An SEM micrograph of the frontal view of a mouse embryo (fetal age 7.75 days) Left: Shh protein is green. Right: Enlarged, cross-section of an embryo at the same developmental day. The dotted line in the micrograph (left) shows the region: Shh antibody reveals Shh. The part that will become the brain (head fold) is followed by the perchordal plate. Shh (in green) that is expressed in the prechordal plate induces midline structure formation.

Research topics

  1. Molecular mechanisms regulating neural stem cells development
  2. Molecular mechanisms regulating regeneration of postnatal neural stem cells
  3. Interaction between neural stem cells and microvascular systems

Selected publications

  1. Shikata Y., Hashimoto H., Okada T., Ellis T., Matsumaru D., Shiroishi T., Ogawa M., Wainwright B. and Motoyama J. Ptch1-mediated dosage-dependent action of Shh signal regulates neural progenitor development at late gestational stages. (2010) Dev. Biol. (in press).
  2. Aoto K., Shikata Y., Imai H., Matsumaru D., Tokunaga T., Shioda S., Yamada G. & Motoyama J. (2009) Mouse Shh is required for prechordal plate maintenance during brain and craniofacial morphogenesis. Dev Biol. 327, 106-120.
  3. Aoto K., Shikata Y., Higashiyama D., Shiota K. & Motoyama J. (2008) Fetal ethanol exposure activates protein kinase A and impairs Shh expression in prechordal mesendoderm cells in the pathogenesis of holoprosencephaly. Birth Defects Res A Clin Mol Teratol. 82, 224-231.
  4. Motoyama J. (2006) Essential roles of Gli3 and sonic hedgehog in pattern formation and developmental anomalies caused by their dysfunction. Congenit Anom. 46, 123-128. Review.
  5. Motoyama J. & Aoto K. Important role of Shh controlling Gli3 functions during the dorsal-ventral patterning of the telencephalon. In Hedgehog-Gli Signaling in Human Disease, Editor: A. Ruiz i Altaba Chapter 14, 177-183 (2006). Landes Bioscience/Eurekah.com, Springer Science+Business Media, Inc. Texas. Review.
  6. Motoyama J., Milenkovic L., Iwama M., Shikata Y., Scott M.P., & Hui CC. (2003) Differential requirement for Gli2 and Gli3 in ventral neural cell fate specification. Dev Biol. 259, 150-161.
  7. Aoto K., Nishimura T., Eto K. & Motoyama J. (2002) Mouse GLI3 regulates Fgf8 expression and apoptosis in the developing neural tube, face, and limb bud. Dev Biol. 251, 320-332.
  8. Motoyama J., Liu J., Mo R., Ding Q., Post M. & Hui CC. (1998) Essential function of Gli2 and Gli3 in the formation of lung, trachea and oesophagus. Nat Genet. 20, 54-57.
  9. Motoyama J., Takabatake T., Takeshima K. & Hui CC. (1998) Ptch2, a second mouse Patched gene is co-expressed with Sonic hedgehog. Nat Genet. 18, 104-106.
  10. Motoyama J., Kitajima K., Kojima M., Kondo S. & Takeuchi T. (1997) Organogenesis of the liver, thymus and spleen is affected in jumonji mutant mice. Mech Dev. 66, 27-37.

Members

Jun Motoyama, Ph.D. (Principal investigator, Professor)
Daisuke Sakai, Ph.D. (Research assistant professor)
Yuki Murakami, Ph.D. (Research assistant professor)

Contact

1-3 Tatara Miyakodani, Kyotanabe-shi, Kyoto 610-0394 Japan
E-mail : jmotoyam@mail.doshisha.ac.jp
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